Antikoagulation bei Patienten mit nichtvalvulärem Vorhofflimmern (nvVHF) und eingeschränkter Nierenfunktion (NI)

Zusammenfassung

Nichtvalvuläres Vorhofflimmern (nvVHF) ist wegen des assoziierten Schlaganfallrisikos eine Hauptindikation der oralen Antikoagulation. Viele dieser Patienten zeigen eine eingeschränkte Nierenfunktion, die das Schlaganfall- und Blutungsrisiko erhöht. Bei Niereninsuffizienz und nvVHF werden Vitamin-K-Antagonisten (VKA) von den Leitlinien aufgrund der heterogenen Studienlage nur zurückhaltend empfohlen – laut Fachinformation sind sie bei manifester Nierenfunktionsstörung kontraindiziert. Neue orale Antikoagulanzien (NOAK) sind bei Patienten mit Niereninsuffizienz ab einer Kreatinin-Clearance (KrCl) von 25 oder 30 ml/min klinisch untersucht und zugelassen, die Faktor-Xa-Inhibitoren können auch bei einer KrCl > 15 ml/min angewendet werden. NOAK zeigen gegenüber VKA ein günstiges Nutzen-Risiko-Profil bei der Reduktion von Schlaganfällen, sonstigen thromboembolischen Ereignissen und Todesfällen einerseits und beim Auftreten von Blutungen andererseits und werden daher von den ESC-Leitlinien empfohlen.

Abstract

Due to the associated risk of stroke, non-valvular atrial fibrillation (nvAF) is a major indication for oral anticoagulation. Many patients suffer from chronic kidney disease (CKD), which increases the risk for stroke and for bleeding. Vitamin K antagonists (VKA) receive only cautious recommendations in guidelines for patients with CKD and nvVHF due to heterogeneous study results; their summaries of product characteristics contain contraindications for patients with manifest CKD. Novel oral anticoagulants (NOACs) have been investigated and are approved in CKD patients with a creatinine clearance (CrCl) ≥ 25 or 30 ml/min, factor Xa inhibitors can be used also if CrCl is > 15 ml/min. NOACs show an advantageous benefit-risk profile compared to VKA in reducing stroke, other thromboembolic events and death on the one hand and occurrence of bleedings on the other, and are recommended by the current ESC guidelines.

Schüsselwörter

NOAK - Niereninsuffizienz - Vorhofflimmern - VKA - Leitlinien

Key words

DOAC - chronic kidney disease - atrial fibrillation - VKA - guidelines

• Literatur

• 1 Turakhia MP, Blankestijn PJ, Carrero JJ. et al. Conference Participants. CKD and arrhythmias: conclusions from the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. EHJ 2018; 39: 2314-2325
• 2 Kraus D, Wanner C. Epidemiologie chronischer Nierenerkrankungen – werden es immer mehr Patienten?. Dtsch Med Wochenschr 2017; 142: 1276-1281
• 3 Wilke T, Groth A, Mueller S. et al. Incidence and prevalence of atrial fibrillation: an analysis based on 8.3 million patients. Europace 2013; 15: 486-493
• 4 Kirchhof P, Benussi S, Kotecha D. ESC Scientific Document Group. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J 2016; 37: 2893-2962
• 5 Spyra A, Daniel D, Thate-Waschke IM. et al. Vorhofflimmern in Deutschland – eine prospektive Krankheitskostenstudie. Dtsch Med Wochenschr 2015; 140: e142-e148
• 6 KDIGO CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 1-150
• 7 Piccini JP, Stevens SR, Chang Y. ROCKET AF Steering Committee and Investigators. et al. Renal dysfunction as a predictor of stroke and systemic embolism in patients with NVAF. Circulation 2013; 127: 224-232
• 8 Goto S, Angchaisuksiri P, Bassand JP. et al. Management and 1-year outcomes of patients with newly diagnosed atrial fibrillation and chronic kidney disease: results from the prospective GARFIELD-AF registry. J Am Heart Assoc 2019; 8 (03) e010510 . doi:10.1161/JAHA.118.010510
• 9 Schlieper G, Schwenger V, Remppis A. et al. Antikoagulation bei Patienten mit chronischer Niereninsuffizienz. Internist 2017; 58: 512-521
• 10 Wanner C, Herzog CA, Turakhia MP. Conference Steering Committee. CKD and arrhythmias: highlights from the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2018; 94: 231-234
• 11 Bonde AN, Lip GY, Kamper AL. et al. Net clinical benefit of antithrombotic therapy in patients with atrial fibrillation and chronic kidney disease: a nationwide observational cohort study. J Am Coll Cardiol 2014; 64: 2471-2482
• 12 Dahal K, Kunwar S, Rijal J. et al. Stroke, major bleeding, and mortality outcomes in warfarin users with atrial fibrillation and chronic kidney disease: a meta-analysis of observational studies. Chest 2016; 149: 951-959
• 13 Van Der Meersch H, De Bacquer D, De Vriese AS. Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial fibrillation: A systematic review and meta-analysis. Am Heart J 2017; 184: 37-46
• 14 Heine GH, Brandenburg V, Schirmer SH. Orale Antikoagulation bei chronischer Nierenerkrankung und Vorhofflimmern. Dtsch Arztebl Int 2018; 115: 287-294
• 15 Böhm M, Ezekowitz MD, Connolly SJ. et al. Changes in renal function in patients with AF – An analysis from the RE-LY trial. JACC 2015; 65: 2481-2493
• 16 Brodsky S, Eikelboom J, Hebert LA. Anticoagulant-related nephropathy. J Am Soc Nephrol 2018; 29: 2787-2793
• 17 Steffel J, Verhamme P, Potpara TS. et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39: 1330-1393
• 18 Mueck W, Lensing AWA, Agnelli G. et al. Rivaroxaban. Population pharmacokinetic analyses in patients treated for acute deep-vein thrombosis and exposure simulations in patients with atrial fibrillation treated for stroke prevention. Clin Pharmacokinet 2011; 50: 675-686
• 19 De Vriese AS, Caluwé R, Bailleul E. et al. Dose-finding study of rivaroxaban in hemodialysis patients. Am J Kidney Dis 2015; 66: 91-98
• 20 Bristol-Myers Squibb. Fachinformation Eliquis. Stand: Juli 2019
• 21 Boehringer Ingelheim. Fachinformation Pradaxa. Stand: Mai 2019
• 22 Fachinformation Lixiana® 60 mg. Stand: Mai 2019
• 23 Fachinformationen Xarelto®. Stand: Juli 2019
• 24 Steinberg BA, Shrader P, Pieper K. et al. Frequency and outcomes of reduced dose non–vitamin K antagonist anticoagulants: results from ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II). J Am Heart Assoc 2018; 7: e007633 . doi:10.1161/JAHA.117.007633
• 25 Yao X, Shah ND, Sangaralingham LR. et al. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol 2017; 69: 2779-2790
• 26 Granger CB, Alexander JH, McMurray JJ. et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981-992
• 27 Bai Y, Deng H, Shantsila A. et al. Rivaroxaban versus dabigatran or warfarin in real-world studies of stroke prevention in atrial fibrillation: systematic review and meta-analysis. Stroke 2017; 48: 970-976
• 28 Hohnloser SH, Basic E, Hohmann C. et al. Effectiveness and safety of non-vitamin K oral anticoagulants in comparison to phenprocoumon: data from 61000 patients with atrial fibrillation. Thromb Haemost 2018; 118: 526-538
• 29 Kimachi M, Furukawa TA, Kimachi K. et al. Direct oral anticoagulants versus warfarin for preventing stroke and systemic embolic events among atrial fibrillation patients with chronic kidney disease. Cochrane Database Syst Rev 2017; 11: CD011373 . doi:10.1002/14651858.CD011373.pub2. Review
• 30 FDA. Apixaban Clinical Review Addendum. December 17, 2012, Im Internet: http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202155Orig1s000MedR.pdf ; Stand: 11.09.2019
• 31 Hohnloser SH, Hijazi Z, Thomas L. et al. Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J 2012; 33: 2821-2830
• 32 Connolly SJ, Ezekowitz MD, Yusuf S. et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139-1151
• 33 Hijazi Z, Hohnloser SH, Oldgren J. et al. Efficacy and safety of dabigatran compared with warfarin in patients with AF in relation to renal function over time (RE-LY). Circulation 2014; 129: 961-970
• 34 Giugliano RP, Ruff CT, Braunwald E. et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093-2104
• 35 Bohula EA, Giugliano RP, Ruff CT. et al. Impact of renal function on outcomes with edoxaban in the ENGAGE AF-TIMI 48 trial. Circulation 2016; 134: 24-36
• 36 Patel MR, Mahaffey KW, Garg J. et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883-891
• 37 Fox KA, Piccini JP, Wojdyla D. et al. Prevention of stroke and SE with rivaroxaban compared with warfarin in patients with NVAF and moderate renal impairment (ROCKET AF). Eur Heart J 2011; 32: 2387-2394
• 38 Bonnemeier H, Kreutz R, Kloss S. et al. ESOC 2019, Mailand, 23.05.19, Poster-Präsentation AS25-066.
• 39 Yao X, Tangri N, Gersh BJ. et al. Renal outcomes in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol 2017; 70: 2621-2632
• 40 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019; 74: 104-132
• 41 Coleman CI, Kreutz R, Sood NA. et al. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis. Am J Med 2019 [Epub ahead of print]
• 42 Siontis KC, Zhang X, Eckard A. et al. Outcomes Associated With Apixaban Use in Patients With End-Stage Kidney Disease and Atrial Fibrillation in the United States. Circulation 2018; 138: 1519-1529
• 43 Bruins Slot KMH, Berge E. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation (Review). Cochrane Database Syst Rev 2018; 3: CD008980 . doi:10.1002/14651858.CD008980.pub3